Inhibition of the PI3K-AKT-MTORC1 axis reduces the burden of the m.3243A>G mtDNA mutation by promoting mitophagy and improving mitochondrial function.

Mitochondrial DNA (mtDNA) encodes genes essential for oxidative phosphorylation. The m.3243A>G mutation causes severe disease, including myopathy, lactic acidosis and stroke-like episodes (MELAS) and is the most common pathogenic mtDNA mutation in humans.

Deubiquitinase USP1 influences the dedifferentiation of mouse pancreatic β-cells.

Loss of insulin-secreting β-cells in diabetes may be either due to apoptosis or dedifferentiation of β-cell mass. The ubiquitin-proteasome system comprising E3 ligase and deubiquitinases (DUBs) controls several aspects of β-cell functions. In this study, screening for key DUBs identified USP1 to be specifically involved in dedifferentiation process.

Paradoxical neuronal hyperexcitability in a mouse model of mitochondrial pyruvate import deficiency.

Neuronal excitation imposes a high demand of ATP in neurons. Most of the ATP derives primarily from pyruvate-mediated oxidative phosphorylation, a process that relies on import of pyruvate into mitochondria occuring exclusively via the mitochondrial pyruvate carrier (MPC). To investigate whether deficient oxidative phosphorylation impacts neuron excitability, we generated a mouse strain carrying a conditional deletion of MPC1, an essential subunit of the MPC, specifically in adult glutamatergic neurons.

Broad activation of the Parkin pathway induces synaptic mitochondrial deficits in early tauopathy.

Mitochondrial defects are a hallmark of early pathophysiology in Alzheimer's disease, with pathologically phosphorylated tau reported to induce mitochondrial toxicity. Mitophagy constitutes a key pathway in mitochondrial quality control by which damaged mitochondria are targeted for autophagy. However, few details are known regarding the intersection of mitophagy and pathologies in tauopathy.

Positioning canine induced pluripotent stem cells (iPSCs) in the reprogramming landscape of naïve or primed state in comparison to mouse and human iPSCs.

Aims: Deriving canine-induced pluripotent stem cells (ciPSCs) have paved the way for developing novel cell-based disease models and transplantation therapies in the dog. Though ciPSCs have been derived in the presence of Leukemia inhibitory factor (LIF) as well in the presence of basic fibroblast growth factor (bFGF), the positioning of ciPSCs in the naïve or the primed state of pluripotency remains elusive. This study aims to understand whether canine iPSCs belong to naïve or prime state in comparison to mouse (m) iPSCs and human (h) iPSCs.

Mitochondrial Superoxide Dismutase Specifies Early Neural Commitment by Modulating Mitochondrial Dynamics.

Studies revealing molecular mechanisms underlying neural specification have majorly focused on the role played by different transcription factors, but less on non-nuclear components. Earlier, we reported mitochondrial superoxide dismutase (SOD2) to be essential for self-renewal and pluripotency of mouse embryonic stem cells (mESCs). In the present study, we found SOD2 to be specifically required for neural lineage, but not the meso- or endoderm specification.

Mitophagy coordination with retrograde transport ensures the integrity of synaptic mitochondria.

Mitochondria sustain various essential functions at synaptic terminals. Synaptic mitochondria deficits have been implicated in early Alzheimer disease (AD) pathophysiology. Mitophagy, a selective autophagy for removal of damaged mitochondria, plays a key role in mitochondrial quality control in neurons.

Mitophagy regulates integrity of mitochondria at synapses and is critical for synaptic maintenance.

Synaptic mitochondria are particularly vulnerable to physiological insults, and defects in synaptic mitochondria are linked to early pathophysiology of Alzheimer's disease (AD). Mitophagy, a cargo-specific autophagy for elimination of dysfunctional mitochondria, constitutes a key quality control mechanism. However, how mitophagy ensures synaptic mitochondrial integrity remains largely unknown.

Cyclosporine A-Mediated IL-6 Expression Promotes Neural Induction in Pluripotent Stem Cells.

Differentiation of pluripotent stem cells (PSCs) to neural lineages has gathered huge attention in both basic research and regenerative medicine. The major hurdle lies in the efficiency of differentiation and identification of small molecules that facilitate neurogenesis would partly circumvent this limitation. The small molecule Cyclosporine A (CsA), a commonly used immunosuppressive drug, has been shown to enhance in vivo neurogenesis.

Dermoid Cyst of Submental Region Mimicking Pilomatricoma.

Diagnosis of midline neck swellings may give a myriad of options, ranging from ranula, thyroglossal duct cyst, cystic hygroma, cystic lymphangioma, epidermoid, dermoid and teratoid cysts to benign or malignant neoplasms of the mucosa or salivary glands and also rare skin appendage tumours like pilomatricoma or pilomatrix carcinoma. Various pitfalls are encountered in diagnosing these midline swellings as most of the features are overlapping. Careful history and examination have to be complemented with other diagnostic aids such as conventional radiography, ultrasonography, aspiration cytology and computed tomography to arrive at a correct diagnosis.

In vitro characterization of design and compressive properties of 3D-biofabricated/decellularized hybrid grafts for tracheal tissue engineering.

Infection or damage to the trachea, a thin walled and cartilage reinforced conduit that connects the pharynx and larynx to the lungs, leads to serious respiratory medical conditions which can often prove fatal. Current clinical strategies for complex tracheal reconstruction are of limited availability and efficacy, but tissue engineering and regenerative medicine approaches may provide viable alternatives. In this study, we have developed a new "hybrid graft" approach that utilizes decellularized tracheal tissue along with a resorbable polymer scaffold, and holds promise for potential clinical applications.

Managing odds in stem cells: insights into the role of mitochondrial antioxidant enzyme MnSOD.

Reactive oxygen species (ROS) have been poised at a straddled state of being beneficiary as well detrimental depending on its threshold levels. Maintaining the homeostasis of ROS is imperative for normal cellular physiology, wherein physiological concentrations of ROS are involved in cell signaling and elevated ROS contribute to the development of various diseases. Superoxide dismutases (SODs), enzymes involved in dismutation of superoxide anion to hydrogen peroxide, arrive as a first line of defense when there is perturbation in the homeostasis of ROS.

Novel role of mitochondrial manganese superoxide dismutase in STAT3 dependent pluripotency of mouse embryonic stem cells.

Leukemia Inhibitory Factor (LIF)/Signal transducer and activator of transcription 3 (STAT3) signaling pathway maintains the stemness and pluripotency of mouse embryonic stem cells (mESCs). Detailed knowledge on key intermediates in this pathway as well as any parallel pathways is largely missing. We initiated our study by investigating the effect of small molecule Curcumin on various signalling pathways essential for self-renewal.

Pericoronal occurrence of cemento-ossifying fibroma: an unexemplified and unusual case report with review of literature.

The Cemento-ossifying fibroma (COF) is an odontogenic neoplasm that is predominantly considered as a fibro osseous lesion of the jaw bone. The histogenetic origin of COF was thought to be derived from the periodontal cells, which have the ability to form fibrous, cementum and osseous tissue. Due to the periodontal cellular origin, the lesion often occurs in the radicular portion of the bicuspid and molar tooth region of the lower jaw.

Making surrogate β-cells from mesenchymal stromal cells: perspectives and future endeavors.

Generation of surrogate β-cells is the need of the day to compensate the short supply of islets for transplantation to diabetic patients requiring daily shots of insulin. Over the years several sources of stem cells have been claimed to cater to the need of insulin producing cells. These include human embryonic stem cells, induced pluripotent stem cells, human perinatal tissues such as amnion, placenta, umbilical cord and postnatal tissues involving adipose tissue, bone marrow, blood monocytes, cord blood, dental pulp, endometrium, liver, labia minora dermis-derived fibroblasts and pancreas.

Osteogenesis imperfecta/lobstein syndrome associated with dentinogenesis imperfecta.

Osteogenesis imperfecta is a collagen related disorder characterized by increased bone fragility and low bone mass. The important oral finding in osteogenesis imperfect is the presence of dentinogenesis imperfecta. This article presents a case of osteogenesis imperfecta (type IV B) with dentinogenesis imperfecta where a 7-year-old girl had opalacent primary teeth associated with severe bone deformity, scoliosis, barrel shaped rib cage, and short stature.

Zic3 enhances the generation of mouse induced pluripotent stem cells.

Zinc finger protein of the cerebellum (Zic)3, a member of Gli family of transcription factors (TFs), is essential for maintaining pluripotency of embryonic stem cells (ESCs) and has been reported to activate TF Nanog in an Oct4/Sox2-independent manner. Previously, we showed that Zic3 (Z), in combination with the Yamanka factors OCT4, SOX2, and KLF4 (OSK), induces neural progenitor-like cells from human fibroblasts. However, a similar combination of TFs (OSKZ) transduced in mouse embryonic fibroblasts resulted in enhanced induced pluripotent stem cells (iPSCs) formation compared with OSK alone, but not neuroprogenitors.

Antimicrobial properties of hemoglobin.

Hemoglobin consists of a heme containing component and a globin unit. It exists as a tetramer with 2 α subunits and 2 β subunits in adults and with 2 α subunits and 2 γ chains in infants. On proteolytic cleavage, hemoglobin breaks down to produce many biologically active compounds, among which are hemocidins, those which exhibit antimicrobial property.

Influence of rifampicin on D.D.S. excretion in urine.

The plasma half-lives and urinary excretion levels of DDS were compared before and during concurrent administration of Rifampicin in 23 cases of active lepromatous leprosy. The plasma half-life of DDS was found to be slightly less during Rifampicin administration. The urinary excretion of DDS was found to be consistently enhanced in all the cases, particularly duotal duration of Rifampicin therapy.